Older people have loss of about 30-50 minutes of sleep per day compared to young people and greater fragmentation of their remaining sleep. They subsequently are more sleepy during the day and nap more often. We hypothesize that this sleep-wake behavior pattern may be due to the loss of about 50% of the neurons in the ventrolateral preoptic nucleus (VLPO) by about 70 years of age. We plan to study the role of partial sleep restriction and fragmentation in older people with 50% VLPO cell loss in a rat model in which partial VLPO lesions will reduce the cell numbers in young (3 mo) and older (21 mo) rats to 50% of that in healthy young rats. In Aim 1, we will study the sleep-wake cycles of these animals with EEG/EMG and will determine the effect of short term acute sleep deprivation on recovery sleep. We predict that these animals, like older humans, will paradoxically tolerate sleep deprivation better than will young, intact animals. In Aim 2, we will examine the effects of chronic partial sleep restriction in young and older rats with 50% VLPO lesions, on performance in a memory test (Morris water maze) and coordination ,task (Rotarod). We predict that a large part of the fall-off in both memory and motor coordination with age will be due to sleep loss. We also expect that the animals with partial VLPO loss will have less impairment due to further acute sleep deprivation, as they will already be near the maximum level of the effect of cumulative sleep loss on cognitive and motor function. In Aim 3, we will examine the effects of chronic sleep restriction in both young and older rats on metabolic function (glucose, triglycerides, insulin, leptin, ghrelin levels) and immune function (interleukin-6, tumor necrosis factor alpha, C-reactive protein levels). We predict that the loss of sleep will cause changes consistent with the Metabolic Syndrome, such as seen in humans with sleep loss and with aging. Finally, in Aim 4 we will examine whether sleep repletion, using a drug that increases the firing of the remaining VLPO neurons, will reverse these deficits in cognitive, motor, metabolic, and immune function that are due to chronic partial sleep restriction. These data will allow us to establish a rat model for human sleep-wake deficits, and to determine the effect of those deficits on cognitive, motor, metabolic, and immune function, independent of age. If sleep repletion can reverse some of these deficits, such treatment may provide a way for improving both sleep and mental and physical health of older people.